Folate nutritional status of infants is usually in delicate balance, particularly in the case of low birthweight infants. Recent clinical studies suggest that breast feeding affords considerable protection against folate deficiency in infancy, which was more common with dried milk formula or liquid cow milk feeding. Although this is partially attributable to folate lost during processing, other factors may be more important. Indeed, it has been calculated that the folate intake of low birthweight infants is unlikely to meet their dietary requirements, as calculated from supplementing formula diets with free folic acid. In recent studies, we have obtained evidence for a factor in breast milk of humans, cows and goats which enhanced folate availability for uptake by isolated intestinal cells. A very high molecular weight binder for such milk proteins was solubilized from intestinal extracts, suggesting that protein-mediated folate absorption may occur in the infant. This project is aimed at defining the components in milk which mediate uptake of bound folate by isolated intestinal cells. The effect of these components on folate digestion, absorption, and transport will be studied. The quality and quantity of folate binder and their enhancement of folate uptake will be studied in milks obtained at different times in the lactation period from different mothers, and the effects of gestational age and maternal age will be documented. Since some commercially purchased milks lacked the enhancing factor, while retaining relatively high folate binding capacity, a further priority will be to study the effects of variations in the commerical processing and storage of milk on factors which affect availability of folate to the infant. Finally, this study will be aimed at isolation and characterization of the intestinal receptor for the factor in milk which enhances folate absorption. The underlying rationale for this study is to gather information which will optimize folate nutrition in the infant at risk.